Off-label Use of Oral Anticoagulants Raises Ischemic Stroke Risk: Study

New research published in JAMA Cardiology indicates that the use of direct oral anticoagulants for left ventricular (LV) thrombi are linked with an increased risk for ischemic stroke and systemic emboli.

“Left ventricular thrombi can arise in patients with ischemic and nonischemic cardiomyopathies,” the authors wrote in their abstract. “Anticoagulation is thought to reduce the risk of stroke or systemic embolism (SSE), but there are no high-quality data on the effectiveness of direct oral anticoagulants for this indication.”

The research team enrolled 514 eligible patients diagnosed with LV thrombi via echocardiography from three tertiary care academic medical centers between 2013 and 2019. The endpoint of interest was clinically apparent SSE.

According to the study results, 300 patients received warfarin and 185 received direct oral anticoagulants (with 64 switching between treatment groups). Median follow-up was 351 days. According to the unadjusted analysis, the use of direct oral anticoagulants (compared with warfarin) and prior SSE were both significantly associated with SSE. After adjustment, there remained a statistically significant relationship between the use of direct oral anticoagulants versus warfarin (and also prior SSE; HR=2.07; 95% CI, 1.17 to 3.66; P=0.01) with new SSE (HR=2.64; 95% CI, 1.28 to 5.43; P =0.01)

“In this multicenter cohort study of anticoagulation strategies for LV thrombi, direct oral anticoagulation treatment was associated with a higher risk of SSE compared with warfarin use, even after adjustment for other factors,” the researchers concluded. “These results challenge the assumption of direct oral anticoagulant equivalence with warfarin for LV thrombi and highlight the need for prospective randomized clinical trials to determine the most effective treatment strategies for LV thrombi.”

An accompanying editorial stressed the need for a clinical trial for off-label uses of this class of drugs.

“Direct oral anticoagulants have been a breakthrough therapy for adults with nonvalvular atrial fibrillation and venous thromboembolic disease, disease states for which these drugs have been approved by the US Food and Drug Administration,” the authors wrote. “However, these therapies are not a panacea. Most notably, warfarin remains the standard of care for those with mechanical valves.”